Gut-microbiota-brain-immune axis (GMBIA) (GMBIA)

The gut-microbiota-brain-immune axis is a complex, bidirectional communication network that integrates the metabolic activity of the intestinal microbiome with the host's central nervous and immune systems. Central to this axis are short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, which are produced by microbial fermentation of non-digestible carbohydrates (Cryan & Dinan, 2012, Nat Rev Neurosci). These metabolites act as signaling molecules by binding to specific G protein-coupled receptors (e.g., FFAR2, FFAR3) and by inhibiting histone deacetylases, thereby influencing the production of host neurotransmitters like serotonin and the secretion of cytokines (Koh et al., 2016, Cell; Yano et al., 2015, Cell). By modulating the systemic inflammatory environment and signaling through the vagus nerve, the axis plays a critical role in maintaining neurological health and immune homeostasis (Smith et al., 2013, Science). Dysregulation of this network is strongly associated with neurodegenerative conditions like Parkinson’s disease and psychiatric disorders such as major depression (Sampson et al., 2016, Cell). Therapeutic strategies targeting this axis include the use of prebiotics, probiotics, and postbiotics to restore a healthy microbial balance and optimize SCFA-mediated signaling.

Other names

Microbiome-gut-brain axisGut-brain axisGut-immune-brain axisSCFA-mediated signaling pathwayMicrobiota-neuro-immune axis

The axis functions through the microbial fermentation of dietary fibers into short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate, which act as ligands for G protein-coupled receptors (GPR41/FFAR3 and GPR43/FFAR2) and as inhibitors of histone deacetylases (HDACs) (Koh et al., 2016, Cell). This signaling triggers the release of neurotransmitters such as serotonin from enterochromaffin cells and modulates the systemic cytokine profile by inducing the differentiation of regulatory T cells (Tregs) and suppressing pro-inflammatory mediators like TNF-alpha and IL-6 (Smith et al., 2013, Science; Yano et al., 2015, Cell). These signals are transmitted to the central nervous system via the vagus nerve or systemic circulation, influencing neuroinflammation and behavior (Cryan & Dinan, 2012, Nat Rev Neurosci).